Trypanosoma brucei brucei, by definition non-infective to man, is morphologically indistinguishable from T.b. rhodesiense, a human pathogen. This difference in infectivity can be correlated with susceptibility to human serum in vitro. Thus, incubation of T.b. brucei in human serum results in loss of infectivity to laboratory animals and cell death, while under the same conditions T.b. rhodesiense remains infective and viable. It is proposed to study the basis for this differential effect of human serum on these two trypanosome species with two main objectives: 1) isolation and purification by standard biochemical fractionation techniques (column chromatography, isoelectric focusing, acrylamide gel electrophoresis) of the trypanocidal serum factor; 2) characterization of the substrate specificity of the trypanocidal factor, i.e., identification of the components of the surface coat and/or plasma membrane which are affected by or necessary for the activity of this substance. Externally located surface proteins, which can be selectively labelled with radioisotopes (e.g., 125I, NaB3H4), of T.b. brucei and T.b. rhodesiense will be compared. Elucidation of the interactions of the trypanocidal factor in human serum with trypanosome surface proteins will contribute to a better understanding of natural immunity and the molecular basis of infectivity.